Rational Design of Constrained Peptides as Protein Interface Inhibitors

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Abstract
The lack of progress in developing targeted therapeutics directed at protein–protein complexes has been due to the absence of well-defined ligand-binding pockets and the extensive intermolecular contacts at the protein–protein interface. Our laboratory has developed approaches to dissect protein–protein complexes focusing on the superfamilies of erbB and tumor necrosis factor (TNF) receptors by the combined use of structural biology and computational biology to facilitate small molecule development. We present a perspective on the development and application of peptide inhibitors as well as immunoadhesins to cell surface receptors performed in our laboratory.
Funding Information
  • Breast Cancer Research Foundation (Mark Greene)
  • National Institutes of Health (R01 CA219034, P50 CA142509)
  • 2016 PCMD Pilot and Feasibility Grant Program (Hongtao Zhang)

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